Pharmacodynamic Study of CK-2017357 in Patients With Generalized Myasthenia Gravis

Phase 2

Terminated

• Conditions: Myasthenia Gravis
• Interventions: Drug: Placebo; Drug: 250 mg CK-2017357; Drug: 500 mg CK-2017357

• Registration Number: NCT01268280
• Lead Sponsor: Cytokinetics

Brief Summary

The primary objective of this early-stage clinical study is to demonstrate an effect of single doses of CK-2017357 on measures of skeletal muscle function and fatigability in patients with generalized myasthenia gravis (MG).

Detailed Description

This study is a Phase II, double-blind, randomized, three-way crossover, placebo-controlled, PD study of CK-2017357 in patients with generalized MG on standard therapy. 36 to 78 patients will be randomized at approximately 15 study centers to one of six different treatment sequences. Each treatment sequence consists of three dosing periods in which patients receive single oral doses of placebo, 250 mg, and 500 mg of CK-2017357. All six treatment sequences will enroll 6 patients. A wash out period of at least 7 days (to a maximum of 10 days) will be employed between the individual doses for each patient. This study is designed to assess the effects of CK-2017357 on the standardized Quantitative Myasthenia Gravis (QMG) score, Manual Muscle Test, Myasthenia Gravis Composite Assessment (MGCA) and Forced Vital Capacity. The pharmacokinetic (PK) and pharmacodynamic (PD) relationship of CK-2017357 after two single doses will be assessed versus placebo.

Study Timeline

• Study Start: 2010-12
• Study First Submitted: 2010-12-28
• Study First Submitted QC: 2010-12-29
• Study First Posted: 2010-12-30
• Primary Completion: 2012-10
• Study Completion: 2012-10
• Status Verified: 2019-09
• Disposition First Submitted: 2019-09-18
• Disposition First Submitted QC: 2019-09-18
• Last Update Submitted: 2019-09-18
• Disposition First Posted: 2019-09-24
• Last Update Posted: 2019-09-24

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 32

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Treatment Sequence 1	Placebo	Dosing Period 1 Placebo; Dosing Period 2 CK-2017357 250 mg; Dosing Period 3 CK-2017357 500 mg
Treatment Sequence 1	250 mg CK-2017357	Dosing Period 1 Placebo; Dosing Period 2 CK-2017357 250 mg; Dosing Period 3 CK-2017357 500 mg
Treatment Sequence 2	Placebo	Dosing Period 1 Placebo; Dosing Period 2 CK-2017357 500 mg; Dosing Period 3 CK-2017357 250 mg
Treatment Sequence 3	Placebo	Dosing Period 1 CK-2017357 250 mg; Dosing Period 2 Placebo; Dosing Period 3 CK-2017357 500 mg
Treatment Sequence 3	250 mg CK-2017357	Dosing Period 1 CK-2017357 250 mg; Dosing Period 2 Placebo; Dosing Period 3 CK-2017357 500 mg
Treatment Sequence 3	500 mg CK-2017357	Dosing Period 1 CK-2017357 250 mg; Dosing Period 2 Placebo; Dosing Period 3 CK-2017357 500 mg
Treatment Sequence 4	Placebo	Dosing Period 1 CK-2017357 250 mg; Dosing Period 2 CK-2017357 500 mg; Dosing Period 3 Placebo
Treatment Sequence 4	250 mg CK-2017357	Dosing Period 1 CK-2017357 250 mg; Dosing Period 2 CK-2017357 500 mg; Dosing Period 3 Placebo
Treatment Sequence 4	500 mg CK-2017357	Dosing Period 1 CK-2017357 250 mg; Dosing Period 2 CK-2017357 500 mg; Dosing Period 3 Placebo
Treatment Sequence 5	Placebo	Dosing Period 1 CK-2017357 500 mg; Dosing Period 2 Placebo; Dosing Period 3 CK-2017357 250 mg
Treatment Sequence 5	250 mg CK-2017357	Dosing Period 1 CK-2017357 500 mg; Dosing Period 2 Placebo; Dosing Period 3 CK-2017357 250 mg
Treatment Sequence 5	500 mg CK-2017357	Dosing Period 1 CK-2017357 500 mg; Dosing Period 2 Placebo; Dosing Period 3 CK-2017357 250 mg
Treatment Sequence 6	Placebo	Dosing Period 1 CK-2017357 500 mg; Dosing Period 2 CK-2017357 250 mg; Dosing Period 3 Placebo
Treatment Sequence 6	250 mg CK-2017357	Dosing Period 1 CK-2017357 500 mg; Dosing Period 2 CK-2017357 250 mg; Dosing Period 3 Placebo
Treatment Sequence 6	500 mg CK-2017357	Dosing Period 1 CK-2017357 500 mg; Dosing Period 2 CK-2017357 250 mg; Dosing Period 3 Placebo
Treatment Sequence 1	500 mg CK-2017357	Dosing Period 1 Placebo; Dosing Period 2 CK-2017357 250 mg; Dosing Period 3 CK-2017357 500 mg
Treatment Sequence 2	250 mg CK-2017357	Dosing Period 1 Placebo; Dosing Period 2 CK-2017357 500 mg; Dosing Period 3 CK-2017357 250 mg
Treatment Sequence 2	500 mg CK-2017357	Dosing Period 1 Placebo; Dosing Period 2 CK-2017357 500 mg; Dosing Period 3 CK-2017357 250 mg

Primary Outcome Measures

Name	Time	Method
Pulmonary Function Test (VC in liters)	1 day	Forced Vital Capacity
Manual Muscle Test (MMT)	1 day	Sum of strength or function values assessed by physician on the neck, shoulder, hip and ankle
Quantitative Myasthenia Gravis score (QMG)	1 day	A quantitative motor assessment of muscular weakness on a scale of 0 to 3 with 0 representing "none" and 3 representing "severe". Muscular assessments included in the overall score are effects on double vision, ptosis, facial muscles, swallowing, speech, outstretched arms and legs, forced vital capacity, hand grip strength, and ability to lift head.

Secondary Outcome Measures

Name	Time	Method
Characterize dose and plasma concentrations of CK-2017357 and QMG	2 days
Characterize dose and plasma concentrations of CK-2017357 and Manual Muscle Test (MMT)	2 days
Number of patients with adverse events	4 weeks
Patient Global Assessment	2 days	Patients answer a single question as to whether they feel the same, better or worse as compared to how they felt pre-dose
Investigator Global Assessment	2 days	Investigator answer a single as question as to whether they think the patient appears the same, better or worse as compared to the patient's status at pre-dose
Characterize dose and plasma concentrations of CK-2017357 and Forced Vital Capacity (FVC)	2 days
Modified MG Symptom Score	2 days	Patients will be asked questions regarding five myasthenia gravis systems including trouble using eyes, trouble eating, difficulty speaking, trouble walking and trouble performing personal grooming needs. Each of the areas is scored 0 (none at all) to 3 (very much) and the overall score combining the score of all five areas on a scale of 0 to 15 with 0 being normal and 15 being severe weakness

Trial Locations

Locations (15)

Drexel University College of Medicine; 🇺🇸 Philadelphia, Pennsylvania, United States

Duke University; 🇺🇸 Durham, North Carolina, United States

Baylor College of Medicine; 🇺🇸 Houston, Texas, United States

The University of Kansas Medical Center; 🇺🇸 Kansas City, Kansas, United States

California Pacific Medical Center; 🇺🇸 San Francisco, California, United States

UCSF - Fresno; 🇺🇸 Fresno, California, United States

Stanford University; 🇺🇸 Stanford, California, United States

Hospital for Special Care; 🇺🇸 New Britain, Connecticut, United States

Johns Hopkins; 🇺🇸 Baltimore, Maryland, United States

Neurocare Center for Research; 🇺🇸 Newton, Massachusetts, United States

University of North Carolina; 🇺🇸 Chapel Hill, North Carolina, United States

West Penn Allegheny Health System; 🇺🇸 Pittsburgh, Pennsylvania, United States

University of Texas Health Science Center; 🇺🇸 San Antonio, Texas, United States

University of California - Irvine; 🇺🇸 Orange, California, United States

University of Virginia Health System; 🇺🇸 Charlottesville, Virginia, United States